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Biomedical subjects

C Streffer

Publications and source records attributed to C Streffer.

At least 127 records · Page 7Linked to original sources
PubMed1991

Repair capacity and kinetics in spheroids from a lung metastasis of a human soft tissue sarcoma: a growth delay study.

Spheroids grown from the human cell line EF8 of a lung metastasis of a human malignant fibrous histiocytoma were given fractionated irradiation with 60Co gamma rays at passages 31 and 32. The mean diameter of the spheroids at the time of treatment was 250 microns. Growth delay was used as the end point in these studies. Two experiments were carried out to determine the capacity and kinetics of repair of sublethal damage. In the first experiment, one, two, and five fractions were given at three or four dose levels with fixed intervals of 360 min. In the second experiment, schedules with two and four dose fractions and intervals of 0, 20, 60, 120, and 360 min were used, each at two dose levels. Data analysis was performed by a direct method based on the alpha/beta model and first-order repair kinetics of radiation damage. In both experiments, the alpha/beta value of EF8 spheroids was estimated to be about 8 (6-10) Gy. The rate constant of repair, mu, and its 95% confidence interval were estimated to be 0.62 (0.40-0.84) 10(-2) min-1, equivalent to a half-time of repair (T1/2) of 112 (83-172) min. A more detailed analysis of the data of the second experiment revealed a significant dependence of the rate constant of repair, mu, on the total radiation effect induced by the fractionated radiation treatments with short overall times. With increasing level of effect, mu decreased. These data indicate that the half-time of recovery of a human tumor can be longer than that of the surrounding normal tissue, in this case lung, at least for a limited range of doses and for some fractionation schedules.

Cobalt Radioisotopes↗
PubMed1991

Micronuclei in human lymphocytes irradiated in vitro or in vivo.

Venous blood from healthy donors or from patients with various lympho- and myeloproliferative diseases was incubated in vitro in the presence of cytochalasin B for the induction of binucleated lymphocytes. The time at which cytochalasin B was added depended on the proliferation rate of the lymphocytes. Proliferation was monitored using a semiautomatic microscope photometer/computer system. The background level of micronuclei in binucleated lymphocytes of the patients before radiotherapy was statistically indistinguishable from that of healthy persons. Blood from both groups was irradiated in vitro for the study of the dose-response relationship. The dose-response curves were very similar up to 3.75 Gy, and a somewhat lower micronucleus frequency was found in lymphocytes of patients after a 5-Gy exposure. These in vitro results were compared with in vivo exposure after total-body irradiation of leukemic patients. Due to heavy medication that accompanied radiation therapy, only two doses (1.25 and 2.5 Gy) could be checked after in vivo exposure. There was no statistically significant difference between in vitro and in vivo results after 1.25 Gy, but a slightly lower number of micronuclei was observed after in vivo exposure to 2.5 Gy.

Adult↗
PubMed1991

Tumor radiosensitivity prediction by the cytokinesis-block micronucleus assay.

An in vivo to in vitro cytokinesis-block micronucleus assay technique using cytochalasin B (Cyt-B) was established in xenografted human and murine tumors, and the correlation between radiosensitivity measured by this assay and that measured by a colony-forming assay was investigated. Tumors were irradiated in situ, excised immediately, and disaggregated to single cells that were plated for the micronucleus and colony-forming assays. Some of the tumor cells were irradiated in vitro rather than in vivo. For the micronucleus assay, Cyt-B (0.5-3 micrograms/ml) was added to dishes soon after plating or in vitro irradiation and the cells were subsequently fixed and stained at intervals (12-144 h). The micronucleus frequency in binucleate cells was evaluated under conditions of maximum yield of the binucleate cells. The micronucleus frequency after irradiation was quite variable depending on the tumor type and the average number of micronuclei per single binucleate cell after 4 Gy ranged from 0.2 to 1.4. The results of in vitro irradiation were not significantly different from those of in vivo irradiation for all tumors. A good correlation was found between the radiosensitivity determined by the micronucleus assay and that found with the colony-forming assay in six human tumors (r = 0.94 approximately 0.98) but not in four murine tumors because of one exceptional tumor. When this tumor was excluded, a correlation was also found for the remaining nine tumors (r = 0.62 approximately 0.96). These results indicated that the cytokinesis-block micronucleus assay has some promise as a rapid predictive assay of radiosensitivity.

Animals↗
PubMed1991

Morphological investigations on the small intestinal mucosa of mouse after mild hyperthermic treatment.

Local hyperthermia, when applied as a therapeutic agent against radio-resistant tumours, can result in serious side effects in adjacent non-tumorous tissue, one especially thermo-sensitive organ being the small intestine. An experimental morphological study was therefore undertaken with mice to investigate whether "mild hyperthermia" (41 degrees C for 15, 30 and 60 min) causes alterations at the mucosa of the small intestine, and if so what are these effects and their likely pathomechanisms. Descriptive light and electron microscopical studies and morphometric evaluations are reported on the jejunal mucosa. The observed changes were most extensive after 60 min of 41 degrees C hyperthermia; but even 30 and 15 min hyperthermic treatment was followed by severe degenerative changes. The epithelium of the basal crypts and the stromal cells seemed to remain morphologically unaffected under these conditions, though the stroma can react with a temporary contraction. No "prime event" in the hyperthermia provoked tissue changes can be deducted from the combined light, electron microscopical, and morphometric studies. Comparing, however, the extent of the effects after mild hyperthermia of 60, 30 and 15 min, respectively, four phases of intestinal alterations due to mild hyperthermia and a likely pathomechanism of this treatment can be defined. The clinical implications of the findings are discussed.

Animals↗
PubMed1990

Cytofluorometric determination of protein-bound thiols and DNA in cell nuclei.

The aim of the present study was to establish a cytofluorometric method for the simultaneous determination of protein-bound sulfhydryl-groups (PSH) and DNA in isolated cell nuclei. DNA was stained with ethidiumbromide and PSH with N-iodoacetyl-N(5-sulfo-1-naphthyl) ethylendiamine (AEDANS). Disulfide groups of nuclear proteins were determined by the same method after reduction with sodium borohydride or thioglycollic acid. The method was established by using nuclei of human lymphocytes, which then served as a biological standard for further investigations of the nuclei of different mammalian cell types: nuclei from mouse liver cells and nuclei from the cells of two human melanoma cell lines. For non-proliferating lymphocytes distinct DNA- and PSH-values could be measured. The PSH-values detected in the nuclei of the other cell types were higher by comparison and varied within the cell cycle; i.e., PSH increased during the S-phase and was almost doubled during the cell generation cycle from G1- to G2-phase. Cell line and cell cycle-dependent variations of nuclear disulfides could also be detected. These results are discussed with respect to their radiobiological implications. In conclusion, thiol groups may represent one factor determining the radiosensitivity of cells, but they are not the only decisive one.

Animals↗
PubMed1990

Lethal and teratogenic effects after exposure to X-rays at various times of early murine gestation.

Various well-defined stages during completion of the second meiotic division and early organogenesis of mouse embryos were X-irradiated with doses of 1-4 Gy (100-400 rad). The major risk was prenatal mortality with radiation sensitivity changing markedly with dependence on the developmental stage irradiated; in the case of day 1 even within hours. The surviving fetuses did show a significantly enhanced frequency of malformations on day 19 of gestation (mostly gastroschisis and some exencephalies). This was true for all stages between days 1 and 8; only sensitivity again changed considerably. The radiation doses used in this study are markedly higher than doses that can be expected from radiation diagnostics, but exposure is in a range comparable to doses that can occur in radiation therapy (e.g., Morbus Hodgkin).

Abnormalities, Radiation-Induced↗
PubMed1990

The vascular architecture of human xenotransplanted tumors: histological, morphometrical, and ultrastructural studies.

This study was designed to examine the vascular system of human xenotransplanted tumors on nude mice with different complementary morphometrical and morphological methods. The vascular system shows a chaotic arrangement. There is an extreme heterogeneity in the vascular distribution and density. Large avascular regions could be identified in several non-necrotic tumors. There was no clear difference in the vascular density between the center and the periphery of the tumors, nor was there any zonal correlation for the distribution of the necrosis. With three-dimensional corrosion casts it could be demonstrated that clusters of vessels were directly beneath areas almost free of vessels. In the center, vessels often form a sinusoidal system with numerous blind ends without clearly discernible endothelial cells. Numerous irregular tumor-cell-lined sinusoids are visible next to endothelial-lined vessels with transmission electron microscopy. With scanning electron microscopy it could be demonstrated that large-calibre endotheliazed vessels were found in the direct vicinity or in the center of non-viable zones. Even large-calibre vessels have a capillary wall structure. Sometimes, a basement membrane cannot be observed at all or only incompletely. There are numerous indications of vascular discontinuities and leaks with a widespread intercellular occurrence of blood cells.

Animals↗
PubMed1990

Diamine oxidase activities in the large bowel mucosa of ulcerative colitis patients.

The term colitis suggests mucosal inflammation as the key event. However, it may be that the disease starts with mucosal hyperproliferation, and inflammation of the impaired mucosa is a succeeding event. Therefore we studied the activity of the intestinal diamine oxidase (DAO) in ulcerative colitis (UC). This enzyme was shown to have a mucosal antiproliferative function. Biopsy specimens of 30 patients having a normal rectosigmoidal mucosa showed a DAO activity of 22.8 nmol/min g. In 12 UC patients the DAO activity was 2.7 nmol/min g (p = 0.01). In 3 patients where UC was in remission the DAO activity was 103, 107 and 208 nmol/min g, indicating an antiproliferative rebound effect. Together with the strongly reduced monoamine oxidase (MAO) activity, the decrease in DAO activity indicates that the large bowel in UC is unable to produce a proliferation terminating substance (probably gamma-aminobutyrate) derived from polyamine metabolism by oxidative deamination (DAO) or by the interconversion pathway (MAO).

Adult↗
PubMed1990

DNA-flow cytometry studies in blood and marrow cells from chronic myelogenous leukemia patients treated with interferon alpha-2b.

Cell cycle distribution in bone marrow and peripheral blood mononucleated cells was studied in patients with chronic myelogenous leukemia (CML) before and during treatment with interferon (IFN) alpha-2b. DNA-flow cytometry with ethidium bromide fluorescence was used. Highly significant differences between mononucleated cells from CML patients and normal controls were seen in peripheral blood but not in bone marrow specimens. Patients achieving hematologic remission during IFN treatment showed a cell cycle distribution in bone marrow cells and peripheral blood cells similar to normal controls.

Bone Marrow↗
PubMed1990

The vasculature of xenotransplanted human melanomas and sarcomas. 3. Morphometric studies.

Morphometric measurements of xenotransplanted tumors allowed the evaluation of vascular distribution and density. The correlation between these two parameters and the amount of necrosis could be determined. A wide range of vascular densities between different tumors was measured. This extreme heterogeneity of vascular distribution and density was seen in the center as well as in the periphery of single tumors. Large avascular regions were identified in several tumors that were not necrotic. The distribution of the necrosis showed no zonal correlation, either. No correlation was observed between the density of vessels and the amount of necrosis.

Animals↗
PubMed1990

Xenografts of five human leiomyosarcomas: radiation response after 60cobalt- and d(14)+Be neutron single doses.

Five permanently established xenograft lines of human soft tissue sarcomas were irradiated with single doses of 5.8 MeV d(14)+Be neutrons and of 60Co rays, respectively, at several dose levels to generate dose response relationships. The tumors were clamped ten minutes prior to and during irradiation to induce uniform hypoxia. All tumours were previously characterized by means of histomorphology, tumour doubling times (DT's), DNA-index and enzyme pattern of the lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (GPD). According to these criteria, three out of five leiomyosarcomas were identical referring to the biopsy of origin, whereas two had changed in successive passages. For the different tumour lines, specific growth delays ranged from 0 to 8.7 after 5.3 Gy neutrons and from 0 to 11.4 after 16 Gy60Co, respectively. In terms of radiosensitivity for different single doses and irradiation qualities, a highly significant overall correlation (rs = 0.82 +/- 0.06) was found for the ranking of the tumours with respect to the growth delay and specific growth delay endpoints. No correlation was found between tumour doubling times and the relative biological effectiveness (RBE). In general, calculated RBE-values decreased with increasing effect level. For the five tumour lines, RBE-values ranged from 1.6 to 12.7 and 2.0 to 4.4 at specific growth delays of 0.5 and 2.0, respectively, under acutely hypoxic conditions. These results indicate a potential advantage for neutrons in a subgroup of human soft tissue sarcomas compared with sparsely ionising irradiation.

Animals↗
PubMed1990

[The effect of adriamycin derivatives in combination with x-rays on MeWo and Be11 cells].

The survival rate of human melanoma cells after X-ray irradiation, treatment with adriamycin derivatives and combined treatment with X-rays and adriamycin derivatives was measured by means of the colony formation test. After X-ray irradiation the melanoma cells showed a high resistance for cell survival. In all tests the Be11-cells were more resistant than MeWo-cells. On combined exposure especially with higher doses of adriamycin derivatives, both cell lines showed the interesting effect, that with increasing concentration the survival rate decreased whereas the D(o) increased. Aclacinomycin-A (ACM-A) and Pirarubicin reduced recovery processes after X-ray irradiation. Therefore Be11-cells showed a four times higher DMF (dosis modifying factor) after ACM-A-treatment than MeWo-cells. Low ACM-A-concentrations combined with low X-ray doses showed on both cell lines supraadditive effects. The effect of pirarubicin was in most of the tests only additive. Compared with ACM-A, pirarubicin was less cytotoxic, showed a larger therapeutic range, caused a smaller D(o) and Dq and had a supraadditive effect in low concentrations on both cell lines. For clinical combined therapy with patients ACM-A is probably better suited than pirarubicin.

Aclarubicin↗
PubMed1990

Glycolytic changes after local hyperthermia in mouse liver and adenocarcinoma.

Glycolytic changes in an adenocarcinoma and in liver of C57B1 mice were determined for up to twelve hours after local hyperthermia at 43 degrees C for 30 min. The metabolites studied included glucose, glucose-6-phosphate, pyruvate, lactate, acetoacetate and beta-hydroxybutyrate. Both the glucose and glucose-6-phosphate levels decreased significantly in liver and tumour and remained low for up to twelve hours. The lactate levels increased slightly immediately after heating but were decreased at later times. However, the hepatic pyruvate levels decreased for up to two hours after heating but increased later reaching control levels. In both liver and tumour the levels of beta-hydroxybutyrate were significantly enhanced immediately after hyperthermia, whereas those of acetoacetate were lowered.

3-Hydroxybutyric Acid↗
PubMed1989

Micronucleus formation in 2-cell embryos after in vitro X-irradiation of mouse spermatozoa.

Mouse spermatozoa were exposed in vitro to various X-ray doses and added to a medium containing superovulated oocytes. The percentage of fertilized oocytes was determined 24 h after sperm addition and 2-cell embryos were investigated for micronucleus formation. The fertilization rate was drastically decreased after exposure to 470 cGy whereas smaller doses had no effect. The dose-response relationship for micronucleus formation per embryo was linear-quadratic and the number of embryos with micronuclei increased linearly with dose. The distribution of micronuclei among 2-cell embryos showed a significant overdispersion relative to the Poisson distribution after sperm irradiation for doses above 188 cGy.

Animals↗
PubMed1989

Combined effects of X rays, Ro 03-8799, and hyperthermia on growth, necrosis, and cell proliferation in a mouse tumor.

A mouse adenocarcinoma was treated with 20 Gy X rays, hyperthermia (30 minutes at 43 degrees C), Ro-03-8799, or a combination of two or three of these agents. Combined treatments increase growth delay in the tumor and this was greatest with the combination of all three modalities. Extensive amounts of necrosis were observed after the combined treatments. This effect was most pronounced after treatment modalities including hyperthermia. On the other hand, the radiation-induced micronucleus formation was more enhanced by the sensitizer than by hyperthermia. After X irradiation and combined treatments with X rays a G2-block was observed in DNA-histograms. Tetraploid cells appeared in large amounts that started DNA synthesis followed by necrosis. From these tumors it was impossible to obtain regular DNA-histograms. Tumor regression is a combined result of reduced cell renewal, increased cytogenetic damage, and development of necrosis.

Adenocarcinoma↗
PubMed1989

Increased chromosome aberration levels in cells from mouse fetuses after zygote X-irradiation.

Cell cultures derived from skin biopsies of mouse fetuses X-irradiated at the zygote stage (2 Gy) were studied for the presence of chromosomal aberrations and micronuclei. In comparison with cells from control, unirradiated fetuses significantly higher spontaneous frequencies of aberrations per 100 metaphases and aberrant metaphases were found in cells which were obtained from normal fetuses and fetuses with gastoschisis after irradiation of the zygote. The proportion of aberrant metaphases in cells from fetuses with gastroschisis but not the frequency of aberrations per 100 cells was significantly higher than in cells from normal fetuses. Spontaneous aberrations were mainly chromatid and chromosome fragments. A significantly higher proportion of cells with micronuclei was observed in cells from fetuses with gastroschisis than in cells from control or normal fetuses after irradiation. The induction of chromosome instability in fetal fibroblasts after zygote irradiation has not previously been reported.

Animals↗